Collating and validating indigenous and local knowledge to apply multiple knowledge systems to an environmental challenge: A case-study of pollinators in India

There is an important role for indigenous and local knowledge in a Multiple Evidence Base to make decisions about the use of biodiversity and its management. This is important both to ensure that the knowledge base is complete (comprising both scientific and local knowledge) and to facilitate participation in the decision making process. We present a novel method to gather evidence in which we used a peer-to-peer validation process among farmers that we suggest is analogous to scientific peer review. We used a case-study approach to trial the process focussing on pollinator decline in India. Pollinator decline is a critical challenge for which there is a growing evidence base, however, this is not the case world–wide. In the state of Orissa, India, there are no validated scientific studies that record historical pollinator abundance, therefore local knowledge can contribute substantially and may indeed be the principle component of the available knowledge base. Our aim was to collate and validate local knowledge in preparation for integration with scientific knowledge from other regions, for the purpose of producing a Multiple Evidence Base to develop conservation strategies for pollinators. Farmers reported that vegetable crop yields were declining in many areas of Orissa and that the abundance of important insect crop pollinators has declined sharply across the study area in the last 10–25 years, particularly Apis cerana, Amegilla sp. and Xylocopa sp. Key pollinators for commonly grown crops were identified; both Apris cerana and Xylocopa sp. were ranked highly as pollinators by farmer participants. Crop yield declines were attributed to soil quality, water management, pests, climate change, overuse of chemical inputs and lack of agronomic expertise. Pollinator declines were attributed to the quantity and number of pesticides used. Farmers suggested that fewer pesticides, more natural habitat and the introduction of hives would support pollinator populations. This process of knowledge creation was supported by participants, which led to this paper being co-authored by both scientists and farmers

Antiplasmodial Activity of [(Aryl)arylsulfanylmethyl]Pyridine▿ †‡

A series of [(aryl)arylsufanylmethyl]pyridines (AASMP) have been synthesized. These compounds inhibited hemozoin formation, formed complexes (KD = 12 to 20 μM) with free heme (ferriprotoporphyrin IX) at a pH close to the pH of the parasite food vacuole, and exhibited antimalarial activity in vitro. The inhibition of hemozoin formation may develop oxidative stress in Plasmodium falciparum due to the accumulation of free heme. Interestingly, AASMP developed oxidative stress in the parasite, as evident from the decreased level of glutathione and increased formation of lipid peroxide, H2O2, and hydroxyl radical (·OH) in P. falciparum. AASMP also caused mitochondrial dysfunction by decreasing mitochondrial potential (ΔΨm) in malaria parasite, as measured by both flow cytometry and fluorescence microscopy. Furthermore, the generation of ·OH may be mainly responsible for the antimalarial effect of AASMP since ·OH scavengers such as mannitol, as well as spin trap α-phenyl-n-tertbutylnitrone, significantly protected P. falciparum from AASMP-mediated growth inhibition. Cytotoxicity testing of the active compounds showed selective activity against malaria parasite with selectivity indices greater than 100. AASMP also exhibited profound antimalarial activity in vivo against chloroquine resistant P. yoelii. Thus, AASMP represents a novel class of antimalarial

Aryl aryl methyl thio arenes prevent multidrug-resistant malaria in mouse by promoting oxidative stress in parasites

We have synthesized a new series of aryl aryl methyl thio arenes (AAMTAs) and evaluated antimalarial activity in vitro and in vivo against drug-resistant malaria. These compounds interact with free heme, inhibit hemozoin formation, and prevent Plasmodium falciparum growth in vitro in a concentration-dependent manner. These compounds concentration dependently promote oxidative stress in Plasmodium falciparum as evident from the generation of intraparasitic oxidants, protein carbonyls, and lipid peroxidation products. Furthermore, AAMTAs deplete intraparasite GSH levels, which is essential for antioxidant defense and survival during intraerythrocytic stages. These compounds displayed potent antimalarial activity not only in vitro but also in vivo against multidrug-resistant Plasmodium yoelii dose dependently in a mouse model. The mixtures of enantiomers of AAMTAs containing 3-pyridyl rings were found to be more efficient in providing antimalarial activity. Efforts have been made to synthesize achiral AAMTAs 17–23 and among them, compound 18 showed significant antimalarial activity in viv

Synthesis and Bio-Evaluation of Human Macrophage Migration Inhibitory Factor Inhibitor to Develop Anti-Inflammatory Agent

Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is involved in the development of an array of inflammatory disorders including rheumatoid arthritis, inflammatory bowel disease, psoriasis, multiple sclerosis and sepsis. The synthesis of MIF-inhibitor is a rationale approach to develop novel anti-inflammatory agent to treat multitude of inflammatory diseases. In this work, we have synthesized and evaluated MIF-inhibitory activity of a series of small molecules containing isoxazoline skeleton. Mode of binding of this inhibitor to human MIF (huMIF) was determined by docking studies. The synthesized molecules inhibit tautomerase activity of huMIF. The anti-inflammatory activity of the most active inhibitor, 4-((3-(4-hydroxy-3-methoxyphenyl)-4, 5-dihydroisoxazol-5-yl) methoxy) benzaldehyde (4b) was evaluated against huMIF-induced inflammation in a cellular model (RAW 264.7 cell). Compound 4b significantly inhibits huMIF-mediated NF-jB translocation to the nucleus, up-regulation of inducible nitric oxide synthase and nitric oxide production in RAW 264.7 cell which are the markers for inflammation. The compound 4b is not cytotoxic as evident from cell viability assay. Hence, the compound 4b has potential to be a novel anti-inflammatory agent

Translocation of heme oxygenase-1 to mitochondria is a novel cytoprotective mechanism against non-steroidal anti-inflammatory drug-induced mitochondrial oxidative stress, apoptosis, and gastric mucosal injury

The mechanism of action of heme oxygenase-1 (HO-1) in mitochondrial oxidative stress (MOS)-mediated apoptotic tissue injury was investigated. MOS-mediated gastric mucosal apoptosis and injury were introduced in rat by indomethacin, a non-steroidal anti-inflammatory drug. Here, we report that HO-1 was not only induced but also translocated to mitochondria during gastric mucosal injury to favor repair mechanisms. Furthermore, mitochondrial translocation of HO-1 resulted in the prevention of MOS and mitochondrial pathology as evident from the restoration of the complex I-driven mitochondrial respiratory control ratio and transmembrane potential. Mitochondrial translocation of HO-1 also resulted in time-dependent inhibition of apoptosis. We searched for the plausible mechanisms responsible for HO-1 induction and mitochondrial localization. Free heme, the substrate for HO-1, was increased inside mitochondria during gastric injury, and mitochondrial entry of HO-1 decreased intramitochondrial free heme content, suggesting that a purpose of mitochondrial translocation of HO-1 is to detoxify accumulated heme. Heme may activate nuclear translocation of NF-E2-related factor 2 to induce HO-1 through reactive oxygen species generation. Electrophoretic mobility shift assay and chromatin immunoprecipitation studies indicated nuclear translocation of NF-E2-related factor 2 and its binding to HO-1 promoter to induce HO-1 expression during gastric injury. Inhibition of HO-1 by zinc protoporphyrin aggravated the mucosal injury and delayed healing. Zinc protoporphyrin further reduced the respiratory control ratio and transmembrane potential and enhanced MOS and apoptosis. In contrast, induction of HO-1 by cobalt protoporphyrin reduced MOS, corrected mitochondrial dysfunctions, and prevented apoptosis and gastric injury. Thus, induction and mitochondrial localization of HO-1 are a novel cytoprotective mechanism against MOS-mediated apoptotic tissue injury

Tryptamine-Gallic Acid Hybrid Prevents Non-steroidal Anti-inflammatory Drug-induced Gastropathy

Non-steroidal anti-inflammatory drugs (NSAIDs) induce gastropathy by promoting mitochondrial pathology, oxidative stress, and apoptosis in gastric mucosal cells. We have synthesized SEGA (3a), a tryptamine-gallic acid hybrid, which prevents NSAID-induced gastropathy by preventing mitochondrial oxidative stress, dysfunction, and apoptosis. SEGA (3a) bears an immense therapeutic potential against NSAID-induced gastropathy. This novel molecule is a significant addition in the discovery of gastroprotective drugs

Mammalian and Avian Larval Schistosomatids in Bangladesh: Molecular Characterization, Epidemiology, Molluscan Vectors, and Occurrence of Human Cercarial Dermatitis

Schistosomiasis is a neglected tropical disease (NTD) caused by blood flukes (Schistosoma spp.). Schistosomatids affect a wide array of vertebrate hosts, including humans. In the present study, multiple species of schistosomatids were identified by isolating schistosomatid cercariae (SC) from naturally infected snails. We also described different biotic and abiotic factors influencing SC infections in snails and reported human cercarial dermatitis (HCD) for the first time in Bangladesh. A total of 22,012 snails of seven species: Lymnaea auricularia, L. luteola, Indoplanorbis exustus, Physa acuta, Viviparus bengalensis, Brotia spp., and Thiara spp., were collected and examined. Among these snails, 581 (2.6%) belonging to five species: L. luteola, L. auricularia, P. acuta, I. exustus, and V. bengalensis, were infected with SC. The rate of infection was the highest for L. luteola (11.1%), followed by L. auricularia (5.3%), and was the lowest for V. bengalensis (0.4%). Prevalence in snails was the highest in September (16.8%), followed by October (9.5%) and November (8.8%), and was the lowest in colder months, such as January (1.8%) and February (2.1%). Infections with schistosomatids were more common in larger snails and snails collected from sunny areas. We confirmed the presence of Schistosoma indicum, S. incognitum, S. nasale, S. spindale, and Trichobilharzia szidati by PCR and sequencing. Through a questionnaire survey, we detected HCD in 214 (53.5%) individuals, and the infection rate was almost equally distributed across all professions. Collectively, the present results suggest that lymnaeid snails are the main vector for Schistosoma spp. prevalent in Bangladesh, and schistosomatids with zoonotic potential are also prevalent

Modelling soil, plant and fertilizer relationship to optimize nutrient management for chilli (<i>Capsicum annuum</i> L) under <i>Alfisols</i> of Southern India

India is the largest producer, consumer and exporter of chilli, which covers 20% of the total area in Southern India. The imbalanced use of chemical fertilizers has detrimental effect on soil physico-chemical and biological properties thereby affecting soil and crop quality. In accordance with this concept, the field experiments were conducted to develop and validate fertilizer prescription equations for chilli crop under rainfed condition. The experiments were conducted in three phases. The basic parameters to develop the targeted yield equations were derived. Further, the developed targeted yield equations were validated in comparison with soil fertility rating approach and general recommended dose (GRD). The results revealed that 4.50, 1.76 and 2.95 kg of N, P2O5, and K2O, respectively were required for producing 100 kg of dry chilli. The STCR approach, with or without FYM, at the targeted yield of 1.30 and 1.00 t ha−1 enhanced the yield over GRD and soil fertility rating approach. The STCR approach also exhibited a higher NPK uptake, use efficiency, microbial biomass carbon and nitrogen, dehydrogenase, acid and alkaline phosphatase activity along with better profitability. Hence, STCR-targeted yield approach could improve the yield, nutrient use efficiency, soil microbial properties and economics of chilli crop.</p